Synthesis of 3′-azido-2′,3′-dideoxy-5-fluorouridine phosphoramidates and evaluation of their anticancer activity

被引：19
|
作者：
Lewandowska, Marta [1 ]
Ruszkowski, Piotr [2 ]
Baraniak, Dagmara [1 ]
Czarnecka, Anna [1 ]
Kleczewska, Natalia [1 ]
Celewicz, Lech [1 ]
机构：
[1] Adam Mickiewicz Univ, Fac Chem, PL-60780 Poznan, Poland
[2] Poznan Univ Med Sci, Dept Pharmacol, PL-60806 Poznan, Poland
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 67卷
关键词：
3; '-Azido-2; 3 '-dideoxy-5-fluorouridine phosphoramidates; Phosphorylation; Cytotoxic activity; Human cancer cell lines: HeLa; KB and MCF-7; NUCLEOSIDE ANALOGS; BIOLOGICAL-ACTIVITY; PYRIMIDINE DEOXYRIBONUCLEOSIDES; ANTIVIRAL ACTIVITY; TRIESTER METHOD; IN-VIVO; 5-FLUORO-2'-DEOXYURIDINE; CELLS; 5-FLUOROURACIL; CYTOTOXICITY;
D O I：
10.1016/j.ejmech.2013.06.047
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of novel 4-chlorophenyl N-alkyl phosphoramidates of 3'-azido-2',3'-dideoxy-5-fluorouridine (12-21) were synthesized by means of phosphorylation of 3'-azido-2',3'-dideoxy-5-fluorouridine (4) with 4-chlorophenyl phosphoroditriazolide (10) followed by a reaction with the appropriate amine. The synthesized phosphoramidates (12-21) were evaluated for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7) using the sulforhodamine B (SRB) assay. The highest activity in all the investigated cancer cells was displayed by phosphoramidate 13 with the N-ethyl substituent and its activity was much higher than that of the parent nucleoside. Also phosphoramidate 17 with the N-propargyl substituent exhibited good activity in all the used cell lines. (C) 2013 Elsevier Masson SAS. All rights reserved.
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收藏
页码：188 / 195
页数：8
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